To determine the independent effects of age and gender on the left ventricular structure and response to upright cycle exercise, we analyzed resting echocardiograms and gated blood pool scans at rest and maximal upright cycle exercise in 95 men and 50 women ages 23 - 86 yrs free of heart disease by history, physical exam, rest and exercise ECG and if > 40 yr old, exercise thallium scan. Left ventricular end-diastolic wall thickness increased with age (r = 0.42) and with body surface area (r = 0.38) in both sexes; after normalization for body size, there was no gender difference in the age-wall thickness relationship. Maximal cycle workload declined similarly with age in men (41%) and women (47%) between the third and ninth decades, although the absolute maximal load achieved was higher in men for any given age. At seated rest age-associated declines in heart rate (HR) and increases in systolic blood pressure (SBP) were observed in both sexes. Resting end diastolic volume index (EDVI) and stroke volume index (SVI) rose with age in men but not in women. At a fixed external workload of 50 watts, heart rate decreased and EDVI, ESVI, and SVI increased with age in men but not in women. In both sexes, maximal heart rate, ejection fraction and cardiac index declined with age whereas end systolic volume index (ESVI) and total systemic vascular resistance (TSVR) increased. Although EDVI at maximal effort increased with age in men but not in women, SVI was not age related in either sex. When men and women younger than 40 years who achieved similar maximal workloads of 125-150 watts were compared across workloads, women had higher heart rates and thence higher cardiac indices than their male counterparts whereas the men had higher systolic blood pressure responses. Fitness-matched older ( > 60 years) men and women demonstrated similar exercise hemodynamics except for a higher heart rate response in the latter. Thus, gender has a significant influence on the age-associated changes in resting and exercise hemodynamics in normal humans. Older men appear to utilize the Frank-Starling mechanism to augment cardiac output more than older women, whereas the latter have a higher heart rate response. However, the apparent gender differences in left ventricular wall thickness are eliminated by normalization for body size.